scholarly journals Recent Advances and Future Prospects in Bacterial and Archaeal Locomotion and Signal Transduction

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Sonia L. Bardy ◽  
Ariane Briegel ◽  
Simon Rainville ◽  
Tino Krell
Keyword(s):  
Signal Transduction ◽  
Protein Complexes ◽  
Model Organism ◽  
Model Organisms ◽  
Content Type ◽  
Research Areas ◽  
Recent Advances ◽  
Wide Range ◽  
Two Component ◽  
Chemosensory Pathways

ABSTRACT The structure and function of two-component and chemotactic signaling and different aspects related to the motility of bacteria and archaea are key research areas in modern microbiology. Escherichia coli is the traditional model organism used to study chemotaxis signaling and motility. However, the recent study of a wide range of bacteria and even some archaea with different lifestyles has provided new insight into the ecophysiology of chemotaxis, which is essential for the establishment of different pathogens or beneficial bacteria in a host. The expanded range of model organisms has also permitted the study of chemosensory pathways unrelated to chemotaxis, multiple chemotaxis pathways within an organism, and new types of chemoreceptors. This research has greatly benefitted from technical advances in the field of cryomicroscopy, which continues to reveal with increasing resolution the complexity and diversity of large protein complexes like the flagellar motor or chemoreceptor arrays. In addition, sensitive instruments now allow an increasing number of experiments to be conducted at the single-cell level, thereby revealing information that is beginning to bridge the gap between individual cells and population behavior. Evidence has also accumulated showing that bacteria have evolved different mechanisms for surface sensing, which appears to be mediated by flagella and possibly type IV pili, and that the downstream signaling involves chemosensory pathways and two-component-system-based processes. Herein, we summarize the recent advances and research tendencies in this field as presented at the latest Bacterial Locomotion and Signal Transduction (BLAST XIV) conference.

scholarly journals Nonhuman primates’ tissue banks: resources for all model organism research

2021 ◽  
Author(s):  
Claire Witham ◽  
Sara Wells
Keyword(s):  
Nonhuman Primates ◽  
Ex Vivo ◽  
Model Organism ◽  
Translation Studies ◽  
Model Organisms ◽  
Laboratory Animals ◽  
Tissue Banks ◽  
Post Mortem ◽  
Wide Range ◽  
Research Programmes

AbstractBiobanks containing tissue and other biological samples from many model organisms provide easy and faster access to ex vivo resources for a wide-range of research programmes. For all laboratory animals, collecting and preserving tissue at post-mortem is an effective way of maximising the benefits of individual animals and potentially reducing the numbers required for experimentation in the future. For primate tissues, biobanks represent the scarcest of these resources but quite possibly those most valuable for preclinical and translation studies.

Histidine kinases in signal transduction pathways of eukaryotes

1997 ◽  
Vol 110 (10) ◽  
pp. 1141-1145 ◽  
Author(s):  
W.F. Loomis ◽  
G. Shaulsky ◽  
N. Wang
Keyword(s):  
Signal Transduction ◽  
Response Regulator ◽  
Signal Transduction Pathways ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Camp Phosphodiesterase ◽  
Wide Range ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Dependent Protein

Autophosphorylating histidine kinases are an ancient conserved family of enzymes that are found in eubacteria, archaebacteria and eukaryotes. They are activated by a wide range of extracellular signals and transfer phosphate moieties to aspartates found in response regulators. Recent studies have shown that such two-component signal transduction pathways mediate osmoregulation in Saccharomyces cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development. Activation of DhkA results in the inhibition of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates the cAMP dependent protein kinase PKA. When PKA is activated late in the differentiation of prespore cells, they encapsulate into spores. There is evidence that this two-component system participates in a feedback loop linked to PKA in prestalk cells such that the signal to initiate encapsulation is rapidly amplified. Such signal transduction pathways can be expected to be found in a variety of eukaryotic differentiations since they are rapidly reversible and can integrate disparate signals.

scholarly journals CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in Myxococcus xanthus

mBio ◽  
2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Jonathan W. Willett ◽  
John R. Kirby
Keyword(s):  
Signal Transduction ◽  
Myxococcus Xanthus ◽  
Complex Signal ◽  
Central Processor ◽  
Two Component System ◽  
Component System ◽  
Chemosensory System ◽  
Content Type ◽  
Phosphorylation State ◽  
Two Component

ABSTRACTMyxococcus xanthusserves as a model organism for development and complex signal transduction. Regulation of developmental aggregation and sporulation is controlled, in part, by the Che3 chemosensory system. The Che3 pathway consists of homologs to two methyl-accepting chemotaxis proteins (MCPs), CheA, CheW, CheB, and CheR but not CheY. Instead, the output for Che3 is the NtrC homolog CrdA, which functions to regulate developmental gene expression. In this paper we have identified an additional kinase, CrdS, which directly regulates the phosphorylation state of CrdA. Both epistasis andin vitrophosphotransfer assays indicate that CrdS functions as part of the Che3 pathway and, in addition to CheA3, serves to regulate CrdA phosphorylation inM. xanthus. We provide kinetic data for CrdS autophosphorylation and demonstrate specificity for phosphotransfer from CrdS to CrdA. We further demonstrate that CheA3 destabilizes phosphorylated CrdA (CrdA~P), indicating that CheA3 likely acts as a phosphatase. Both CrdS and CheA3 control developmental progression by regulating the phosphorylation state of CrdA~P in the cell. These results support a model in which a classical two-component system and a chemosensory system act synergistically to control the activity of the response regulator CrdA.IMPORTANCEWhile phosphorylation-mediated signal transduction is well understood in prototypical chemotaxis and two-component systems (TCS), chemosensory regulation of alternative cellular functions (ACF) has not been clearly defined. The Che3 system inMyxococcus xanthusis a member of the ACF class of chemosensory systems and regulates development via the transcription factor CrdA (chemosensoryregulator ofdevelopment) (K. Wuichet and I. B. Zhulin, Sci. Signal. 3:ra50, 2010; J. R. Kirby and D. R. Zusman, Proc. Natl. Acad. Sci. U. S. A. 100:2008–2013, 2003). We have identified and characterized a homolog of NtrB, designated CrdS, capable of specifically phosphorylating the NtrC homolog CrdA inM. xanthus. Additionally, we demonstrate that the CrdSA two-component system is negatively regulated by CheA3, the central processor within the Che3 system ofM. xanthus. To our knowledge, this study provides the first example of an ACF chemosensory system regulating a prototypical two-component system and extends our understanding of complex regulation of developmental signaling pathways.

scholarly journals Cumate-Inducible Gene Expression System for Sphingomonads and Other Alphaproteobacteria

2013 ◽  
Vol 79 (21) ◽  
pp. 6795-6802 ◽  
Author(s):  
Andreas Kaczmarczyk ◽  
Julia A. Vorholt ◽  
Anne Francez-Charlot
Keyword(s):  
Gene Expression ◽  
Caulobacter Crescentus ◽  
Paracoccus Denitrificans ◽  
Expression System ◽  
Model Organisms ◽  
Inducible Gene Expression ◽  
Gene Expression System ◽  
Content Type ◽  
Wide Range ◽  
Inducible Gene

ABSTRACTTunable promoters represent a pivotal genetic tool for a wide range of applications. Here we present such a system for sphingomonads, a phylogenetically diverse group of bacteria that have gained much interest for their potential in bioremediation and their use in industry and for which no dedicated inducible gene expression system has been described so far. A strong, constitutive synthetic promoter was first identified through a genetic screen and subsequently combined with the repressor and the operator sites of thePseudomonas putidaF1cym/cmtsystem. The resulting promoter, termed PQ5, responds rapidly to the inducer cumate and shows a maximal induction ratio of 2 to 3 orders of magnitude in the different sphingomonads tested. Moreover, it was also functional in otherAlphaproteobacteria, such as the model organismsCaulobacter crescentus,Paracoccus denitrificans, andMethylobacterium extorquens. In the noninduced state, expression from PQ5is low enough to allow gene depletion analysis, as demonstrated with the essential genephyPofSphingomonassp. strain Fr1. A set of PQ5-based plasmids has been constructed allowing fusions to affinity tags or fluorescent proteins.

scholarly journals Quinazoline-Based Antivirulence Compounds Selectively Target Salmonella PhoP/PhoQ Signal Transduction System

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
María Ayelén Carabajal ◽  
Christopher R. M. Asquith ◽  
Tuomo Laitinen ◽  
Graham J. Tizzard ◽  
Lucía Yim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Catalytic Domain ◽  
Kinase Inhibitor ◽  
Adaptive Responses ◽  
Antibacterial Compounds ◽  
Content Type ◽  
Two Component ◽  
Serovar Typhimurium

ABSTRACT The rapid emergence of multidrug resistance among bacterial pathogens has become a significant challenge to human health in our century. Therefore, development of next-generation antibacterial compounds is an urgent need. Two-component signal transduction systems (TCS) are stimulus-response coupling devices that allow bacteria to sense and elaborate adaptive responses to changing environmental conditions, including the challenges that pathogenic bacteria face inside the host. The differential presence of TCS, present in bacteria but absent in the animal kingdom, makes them attractive targets in the search for new antibacterial compounds. In Salmonella enterica, the PhoP/PhoQ two-component system controls the expression of crucial phenotypes that define the ability of the pathogen to establish infection in the host. We now report the screening of 686 compounds from a GlaxoSmithKline published kinase inhibitor set in a high-throughput whole-cell assay that targets Salmonella enterica serovar Typhimurium PhoP/PhoQ. We identified a series of quinazoline compounds that showed selective and potent downregulation of PhoP/PhoQ-activated genes and define structural attributes required for their efficacy. We demonstrate that their bioactivity is due to repression of the PhoQ sensor autokinase activity mediated by interaction with its catalytic domain, acting as competitive inhibitors of ATP binding. While noncytotoxic, the hit molecules exhibit antivirulence effect by blockage of S. Typhimurium intramacrophage replication. Together, these features make these quinazoline compounds stand out as exciting leads to develop a therapeutic intervention to fight salmonellosis.

scholarly journals Two-Component Signal Transduction Systems in the Human Pathogen Streptococcus agalactiae

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Lamar Thomas ◽  
Laura Cook
Keyword(s):  
Signal Transduction ◽  
Streptococcus Agalactiae ◽  
Metabolic Regulation ◽  
Invasive Infection ◽  
Older Individuals ◽  
Content Type ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Group B ◽  
Signal Transduction Systems

ABSTRACT Streptococcus agalactiae (group B Streptococcus [GBS]) is an important cause of invasive infection in newborns, maternal women, and older individuals with underlying chronic illnesses. GBS has many mechanisms to adapt and survive in its host, and these mechanisms are often controlled via two-component signal transduction systems. In GBS, more than 20 distinct two-component systems (TCSs) have been classified to date, consisting of canonical TCSs as well as orphan and atypical sensors and regulators. These signal transducing systems are necessary for metabolic regulation, resistance to antibiotics and antimicrobials, pathogenesis, and adhesion to the mucosal surfaces to colonize the host. This minireview discusses the structures of these TCSs in GBS as well as how selected systems regulate essential cellular processes such as survival and colonization. GBS contains almost double the number of TCSs compared to the closely related Streptococcus pyogenes and Streptococcus pneumoniae, and while research on GBS TCSs has been increasing in recent years, no comprehensive reviews of these TCSs exist, making this review especially relevant.

scholarly journals Cyclic Di-GMP and VpsR Induce the Expression of Type II Secretion in Vibrio cholerae

2017 ◽  
Vol 199 (19) ◽  
Author(s):  
Rudolph E. Sloup ◽  
Ashley E. Konal ◽  
Geoffrey B. Severin ◽  
Michelle L. Korir ◽  
Mira M. Bagdasarian ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Protein Complexes ◽  
Second Messenger ◽  
Type Ii Secretion ◽  
Type Ii ◽  
Secretion Systems ◽  
Content Type ◽  
Severe Diarrhea ◽  
Wide Range ◽  
Genes Encoding

ABSTRACT Vibrio cholerae is a human pathogen that alternates between growth in environmental reservoirs and infection of human hosts, causing severe diarrhea. The second messenger cyclic di-GMP (c-di-GMP) mediates this transition by controlling a wide range of functions, such as biofilms, virulence, and motility. Here, we report that c-di-GMP induces expression of the extracellular protein secretion (eps) gene cluster, which encodes the type II secretion system (T2SS) in V. cholerae. Analysis of the eps genes confirmed the presence of two promoters located upstream of epsC, the first gene in the operon, one of which is induced by c-di-GMP. This induction is directly mediated by the c-di-GMP-binding transcriptional activator VpsR. Increased expression of the eps operon did not impact secretion of extracellular toxin or biofilm formation but did increase expression of the pseudopilin protein EpsG on the cell surface. IMPORTANCE Type II secretion systems (T2SSs) are the primary molecular machines by which Gram-negative bacteria secrete proteins and protein complexes that are folded and assembled in the periplasm. The substrates of T2SSs include extracellular factors, such as proteases and toxins. Here, we show that the widely conserved second messenger cyclic di-GMP (c-di-GMP) upregulates expression of the eps genes encoding the T2SS in the pathogen V. cholerae via the c-di-GMP-dependent transcription factor VpsR.

scholarly journals Identification of Proteins Likely To Be Involved in Morphogenesis, Cell Division, and Signal Transduction in Planctomycetes by Comparative Genomics

2012 ◽  
Vol 194 (23) ◽  
pp. 6419-6430 ◽  
Author(s):  
Christian Jogler ◽  
Jost Waldmann ◽  
Xiaoluo Huang ◽  
Mareike Jogler ◽  
Frank Oliver Glöckner ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Division ◽  
Model Organisms ◽  
Genetic Studies ◽  
Content Type ◽  
Life Styles ◽  
Membrane Bound ◽  
Guilt By Association ◽  
Complex Signaling ◽  
Signal Transduction Systems

ABSTRACTMembers of thePlanctomycetesclade share many unusual features for bacteria. Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and FtsZ, they divide by polar budding, and they are capable of endocytosis. Planctomycete genomes have remained enigmatic, generally being quite large (up to 9 Mb), and on average, 55% of their predicted proteins are of unknown function. Importantly, proteins related to the unusual traits ofPlanctomycetesremain largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in an effort to predict proteins that are likely to be involved in compartmentalization, cell division, and signal transduction. We used three complementary strategies. First, we defined thePlanctomycetescore genome and subtracted genes of well-studied model organisms. Second, we analyzed the gene content and synteny of morphogenesis and cell division genes and combined both methods using a “guilt-by-association” approach. Third, we identified signal transduction systems as well as sigma factors. These analyses provide a manageable list of candidate genes for future genetic studies and provide evidence for complex signaling in thePlanctomycetesakin to that observed for bacteria with complex life-styles, such asMyxococcus xanthus.

scholarly journals The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Jennifer K. Teschler ◽  
Andrew T. Cheng ◽  
Fitnat H. Yildiz
Keyword(s):  
Signal Transduction ◽  
Vibrio Cholerae ◽  
Histidine Kinase ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Response Regulator ◽  
Systematic Analysis ◽  
Content Type ◽  
Two Component ◽  
Two Component Signal Transduction

ABSTRACT Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium Vibrio cholerae is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in V. cholerae biofilm formation. We determined that 7 RRs impacted the expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates the expression of key structural and regulatory biofilm genes in V. cholerae. vxrB is part of a 5-gene operon, which contains the cognate HK vxrA and three genes of unknown function. Strains carrying ΔvxrA and ΔvxrB mutations are deficient in biofilm formation, while the ΔvxrC mutation enhances biofilm formation. The overexpression of VxrB led to a decrease in motility. We also observed a small but reproducible effect of the absence of VxrB on the levels of cyclic di-GMP (c-di-GMP). Our work reveals a new function for the Vxr TCS as a regulator of biofilm formation and suggests that this regulation may act through key biofilm regulators and the modulation of cellular c-di-GMP levels. IMPORTANCE Biofilms play an important role in the Vibrio cholerae life cycle, providing protection from environmental stresses and contributing to the transmission of V. cholerae to the human host. V. cholerae can utilize two-component systems (TCS), composed of a histidine kinase (HK) and a response regulator (RR), to regulate biofilm formation in response to external cues. We performed a systematic analysis of V. cholerae RRs and identified a new regulator of biofilm formation, VxrB. We demonstrated that the VxrAB TCS is essential for robust biofilm formation and that this system may regulate biofilm formation via its regulation of key biofilm regulators and cyclic di-GMP levels. This research furthers our understanding of the role that TCSs play in the regulation of V. cholerae biofilm formation.

scholarly journals A Novel Two-Component System, GluR-GluK, Involved in Glutamate Sensing and Uptake in Streptomyces coelicolor

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Lei Li ◽  
Weihong Jiang ◽  
Yinhua Lu
Keyword(s):  
Signal Transduction ◽  
Glutamate Uptake ◽  
Streptomyces Coelicolor ◽  
Signal Transduction Pathway ◽  
Antibiotic Biosynthesis ◽  
Transduction Pathway ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component

ABSTRACT Two-component systems (TCSs), the predominant signal transduction pathways employed by bacteria, play important roles in physiological metabolism in Streptomyces. Here, a novel TCS, GluR-GluK (encoded by SCO5778-SCO5779), which is located divergently from the gluABCD operon encoding a glutamate uptake system, was identified as being involved in glutamate sensing and uptake as well as antibiotic biosynthesis in Streptomyces coelicolor. Under the condition of minimal medium (MM) supplemented with different concentrations of glutamate, deletion of the gluR-gluK operon (gluR-K) resulted in enhanced actinorhodin (ACT) but reduced undecylprodigiosin (RED) and yellow type I polyketide (yCPK) production, suggesting that GluR-GluK plays a differential role in antibiotic biosynthesis. Furthermore, we found that the response regulator GluR directly promotes the expression of gluABCD under the culture condition of MM with a high concentration of glutamate (75 mM). Using the biolayer interferometry assay, we demonstrated that glutamate acts as the direct signal of the histidine kinase GluK. It was therefore suggested that upon sensing high concentrations of glutamate, GluR-GluK would be activated and thereby facilitate glutamate uptake by increasing gluABCD expression. Finally, we demonstrated that the role of GluR-GluK in antibiotic biosynthesis is independent of its function in glutamate uptake. Considering the wide distribution of the glutamate-sensing (GluR-GluK) and uptake (GluABCD) module in actinobacteria, it could be concluded that the GluR-GluK signal transduction pathway involved in secondary metabolism and glutamate uptake should be highly conserved in this bacterial phylum. IMPORTANCE In this study, a novel two-component system (TCS), GluR-GluK, was identified to be involved in glutamate sensing and uptake as well as antibiotic biosynthesis in Streptomyces coelicolor. A possible GluR-GluK working model was proposed. Upon sensing high glutamate concentrations (such as 75 mM), activated GluR-GluK could regulate both glutamate uptake and antibiotic biosynthesis. However, under a culture condition of MM supplemented with low concentrations of glutamate (such as 10 mM), although GluR-GluK is activated, its activity is sufficient only for the regulation of antibiotic biosynthesis. To the best of our knowledge, this is the first report describing a TCS signal transduction pathway for glutamate sensing and uptake in actinobacteria.

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